Huntington disease (HD) is an autosomal dominant neurodegenerative disorder that affects about one in every 10,000 individuals in Europe and North America. Although the gene responsible for the disease was identified six years ago, its biological function is still unknown. We have identified and sequenced the homolog of HD in the fruit fly Drosophila melanogaster. The fly is a particularly attractive model system because it is amenable to developmental analysis and genetic manipulation. To gain further insight into the normal function of the HD protein, the cellular and subcellular localization of Drospohila HD will be characterized using antibodies that we are currently generating. A P-element mutagenesis will also be initiated to generate loss-of-function mutations in Drosophila HD. Finally, a set of experiments has been proposed in which potential biochemical and genetic interactions between Drosophila HD and the fly homologs for HAP1, HIP-1, and HIP-2 will be investigated.